Luo Jing, Wang Zhongqiu, Huang Jianfeng, Yao Yu, Sun Qi, Wang Jie, Shen Yi, Xu Lin, Ren Binhui
Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Cancer Sci. 2018 Feb;109(2):317-329. doi: 10.1111/cas.13453. Epub 2017 Dec 20.
Esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal cancer, is one of the most common digestive tumors worldwide. In this study, we confirmed that HOXC13, a member of the homeobox HOXC gene family, was significantly upregulated in ESCC and its overexpression was associated with poorer clinical characteristics and worse prognosis. Moreover, knockdown of HOXC13 inhibited proliferation and induced apoptosis of ESCC through upregulating CASP3. ChIP analysis revealed that HOXC13 repressed transcription of CASP3 through directly targeting the promotor region of CASP3. We also found that miR-503 downregulated HOXC13, by directly targeting its 3'UTR, and inhibited proliferation of ESCC. In conclusion, our study demonstrates that HOXC13, which is directly targeted by miR-503, promotes proliferation and inhibits apoptosis of ESCC through repressing transcription of CASP3.
食管鳞状细胞癌(ESCC)是食管癌的主要亚型,是全球最常见的消化肿瘤之一。在本研究中,我们证实了同源盒HOXC基因家族成员HOXC13在ESCC中显著上调,其过表达与较差的临床特征和更差的预后相关。此外,敲低HOXC13通过上调CASP3抑制ESCC的增殖并诱导其凋亡。染色质免疫沉淀分析显示,HOXC13通过直接靶向CASP3的启动子区域来抑制其转录。我们还发现,miR-503通过直接靶向HOXC13的3'非翻译区来下调HOXC13,并抑制ESCC的增殖。总之,我们的研究表明,被miR-503直接靶向的HOXC13通过抑制CASP3的转录来促进ESCC的增殖并抑制其凋亡。